Scientists often look askance at their colleagues whose research appears too strongly focused on a single gene or gene product. We are supposed to be interested in the “big picture” and excessive zeal in pursuit of a single pixel might seem to border on an obsession that is likely to yield only details. However as this volume of Current Topics in Microbiology and Immunology demonstrates, this is certainly not the case for myc. Intense study of this en- matic proto-oncogene over the last twenty years has only broadened our view of its functions and led to insights into mechanisms relating to transcriptional regulation as well as to cell growth, proliferation, differentiation, apoptosis and organismal development. The myc gene originally came to light as a retroviral oncogene (v-myc) associated with a wide range of acute neoplasms. It was later shown to be a virally transduced cellular gene (c-myc) which is a member of family of on- genes (c-myc,N-myc,L-myc). These family members are themselves subject to a bewildering assortment of genetic rearrangements associated with many different types of tumors derived from many different types of cells. These rearrangements (including chromosomal translocation, viral integration, and gene ampli?cation) act to uncouple expression of the myc family genes from their normal physiological regulators. The chapter by LIU and LEVENS - scribes the key pathways leading to regulation of myc expression, showing that such regulation occurs at several different levels and through multiple mechanisms.
Intense study of the enigmatic myc proto-oncogene over the last 20 years has broadened our view of its functions and led to insights into transcriptional regulation as well as cancer etiology, cell proliferation, apoptosis, and organismal development. How can one gene be involved in so many aspects of cellular behavior? Of particular interest is the fact that the Myc protein functions as part of a network (comprising Myc, Max, and Mad proteins) whose specific interactions direct transcriptional activation or repression of a large number of target genes. The chapters in this volume examine both molecular and biological aspects of the Myc/Max/Mad network. Included are contributions concerning the regulation of its expression, the mechanisms underlying its diverse transcriptional activities, the structural bases for its critical interactions, and the nature of its target genes. Other chapters explore the evolution of the network, its role in development and genomic instability, and the evidence for a parallel transcriptional network. Overall, this volume provides a broad and current overview of research on a crucial group of transcription factors.
Preface.- Making Myc.- Transcriptionsl Activation by the Myc Oncoprotein.- Mechanisms of Transcriptional Repression by Myc.- The Mad Side of the Max Network: Antagonising the Function of Myc and More.- Structural Aspects of Interactions within the Myc/Max/Mad Network.- Myc Target Transcriptomes.- c-Myc, Genome Instability, and Tumorigenesis: The Devil is in the Details .- Lessons Learned from Myc/Max/Mad Knockout Mice.- Myc/Max/Mad in Invertebrates. The Evolution of the Max Network.- The Mix Network: Evidence for a Parallel Max-like Transcriptional Network that Regulates Energy Metabolism.- Subject Index